Heparin and heparan sulfate glycosaminoglycans are complex acidic polysaccharides that are involved in a variety of physiological and pathological conditions. Advances in different areas of biology have elucidated the potential roles of HSGAGs in key biological processes (Casu and Lindahl, 2001; Lindahl, 2000; Sasisekharan and Venkataraman, 2000; Shriver et al., 2002) including thrombosis (Petitou et al., 1999), angiogenesis (Sasisekharan et al., 1997), viral invasion (Chen et al., 1997; Fry et al., 1999; Shukla et al., 1999) and tumor growth (Hulett et al., 1999; Vlodavsky et al., 1999; Liu et al. 2002). The repeat unit of a HSGAG polymer is a disaccharide comprising a uronic acid (U), which can exist in two different epimeric forms—α-L-iduronic (I) or β-D-glucuronic (G), linked 1→4 to a α-D-glucosamine residue (A). There are variations within the disaccharide unit in the form of sulfation at the 2-O position of the uronic acid, 3-O and 6-O position of the glucosamine and sulfation or acetylation of the N-position of the glucosamine (Casu and Lindahl, 2001).
Perhaps the best studied structure-activity relationships in HSGAGs is a pentasaccharide sequence in heparin that specifically binds to and activates antithrombin-III thereby playing an inhibitory role in the blood coagulation cascade (Bourin and Lindahl, 1993). Heparin and its derivatives, low molecular weight heparins (LMWHs), are the most widely used clinical agents for prevention of deep vein thrombosis after surgery (Breddin, 2000) and for prevention of myocardial infarction after coronary invasion procedures (Cohen, 1999). Based on the anticoagulant properties of heparin, new therapeutic applications of heparin are being envisaged (Rosenberg, 2001). A synthetic version of the pentasaccharide has been used as an antithrombotic drug (Turpie et al, 2001).
In order to understand the structure-activity relationship of HSGAGs, several analytical tools have been developed for sequencing oligosaccharides which include gel electrophoresis (Turnbull et al., 1999), HPLC (Vives et al., 1999), matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) (Venkataraman et al., 1999) and nanoelectrospray mass spectrometry (Pope et al., 2001). These analytical tools have been applied to dissect the HSGAG oligosaccharide into smaller fragments using a battery of depolymerizing enzymes and other chemical methods and determining the sequence of the oligosaccharides based on specific properties of the smaller fragments (Kreuger et al. 2001).